An aPPARent Functional Consequence in Skeletal Muscle Physiology via Peroxisome Proliferator-Activated Receptors

Phua, Wendy Wen Ting; Wong, Melissa Xin Yu; Liao, Ziqi; Tan, Nguan Soon

doi:10.3390/ijms19051425

Cited by 59 publications

(60 citation statements)

References 221 publications

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“…Thiazolidinediones target PPAR-γ. PPAR-γ are ligand activated transcription factors and activation of PPAR-γ results in insulin sensitization and increases glucose metabolism [181,182]. Thiazolidinediones work by making the adipocytes, liver and muscle cells more sensitive to insulin and by conserving the β-cell function.…”

Section: Treatment Of Pre-diabetesmentioning

confidence: 99%

From Pre-Diabetes to Diabetes: Diagnosis, Treatments and Translational Research

et al. 2019

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Diabetes, a silent killer, is one of the most widely prevalent conditions of the present time. According to the 2017 International Diabetes Federation (IDF) statistics, the global prevalence of diabetes among the age group of 20–79 years is 8.8%. In addition, 1 in every 2 persons is unaware of the condition. This unawareness and ignorance lead to further complications. Pre-diabetes is the preceding condition of diabetes, and in most of the cases, this ultimately leads to the development of diabetes. Diabetes can be classified into three types, namely type 1 diabetes, type 2 diabetes mellitus (T2DM) and gestational diabetes. The diagnosis of both pre-diabetes and diabetes is based on glucose criteria; the common modalities used are fasting plasma glucose (FPG) test and oral glucose tolerance test (OGTT). A glucometer is commonly used by diabetic patients to measure blood glucose levels with fast and rather accurate measurements. A few of the more advanced and minimally invasive modalities include the glucose-sensing patch, SwEatch, eyeglass biosensor, breath analysis, etc. Despite a considerable amount of data being collected and analyzed regarding diabetes, the actual molecular mechanism of developing type 2 diabetes mellitus (T2DM) is still unknown. Both genetic and epigenetic factors are associated with T2DM. The complications of diabetes can predominantly be classified into two categories: microvascular and macrovascular. Retinopathy, nephropathy, and neuropathy are grouped under microvascular complications, whereas stroke, cardiovascular disease, and peripheral artery disease (PAD) belong to macrovascular complications. Unfortunately, until now, no complete cure for diabetes has been found. However, the treatment of pre-diabetes has shown significant success in preventing the further progression of diabetes. To prevent pre-diabetes from developing into T2DM, lifestyle intervention has been found to be very promising. Various aspects of diabetes, including the aforementioned topics, have been reviewed in this paper.

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Section: Treatment Of Pre-diabetesmentioning

confidence: 99%

From Pre-Diabetes to Diabetes: Diagnosis, Treatments and Translational Research

et al. 2019

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“…A considerable number of studies have also found that metformin decreases fasting plasma glucose (PG) concentration and hemoglobin A1c by conserving the β-cell function or by decreasing liver glucose production (hepatic gluconeogenesis) (181)(182)(183)(184). Also, thiazolidinediones can promote insulin sensitivity, increase glucose metabolism, and preserve the β-cell function through activating PPAR-γ (185,186). Meanwhile, they can reduce plasma free fatty acid and intramyocellular lipid content to increase insulin sensitivity and redistribute fats from visceral to subcutaneous adipose to alleviate diabetes.…”

Section: Pharmacological Intervention For Sarcopenic Obesity and Diabmentioning

confidence: 99%

Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments

et al. 2020

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Sarcopenic obesity and diabetes are two increasing health problems worldwide, which both share many common risk factors, such as aging, and general obesity. The pathogenesis of sarcopenic obesity includes aging, physical inactivity, malnutrition, low-grade inflammation, insulin resistance, and hormonal changes. Nevertheless, there are two major reasons to cause diabetes: impaired insulin secretion and impaired insulin action. Furthermore, the individual diagnosis of obesity and sarcopenia should be combined to adequately define sarcopenic obesity. Also, the diagnosis of diabetes includes fasting plasma glucose test (FPG), 2-h oral glucose tolerance test (OGTT), glycated hemoglobin (A1C), and random plasma glucose coupled with symptoms. Healthy diet and physical activity are beneficial to both sarcopenic obesity and diabetes, but there are only recommended drugs for diabetes. This review consolidates and discusses the latest research in pathogenesis, diagnosis, and treatments of diabetes and sarcopenic obesity.

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“…Since fatty acids and their derivatives are agonists of PPARs [31], we asked if FoxA2 expression could be regulated by PPARβ/δ, the predominant PPAR isotype in skeletal muscle [13]. GW501516 (GW), a highly selective PPARβ/δ agonist, increased the mRNA and protein levels of FoxA2 in C2C12 myotubes in a dose-and time-dependent manner ( Figure 3A,B).…”

Section: Pparβ/δ Upregulates Foxa2 Expression In C2c12 Cellsmentioning

confidence: 99%

“…They are activated by endogenous ligands, such as free fatty acids and their derivatives, and by a variety of synthetic drugs used in the treatment of metabolic syndrome and type 2 diabetes [10,11]. PPARβ/δ is the predominant isotype in skeletal muscle and its activation increases lipid uptake and catabolism via β-oxidation [12], along with a shift towards oxidative fibers, which enhances oxidative capacity and promotes running endurance, leading to an overall reduction in body fat [13][14][15]. Conversely, selective PPARβ/δ ablation in skeletal muscle leads to lower oxidative capacity in the fibers, resulting in obesity and diabetes [16].…”

Section: Introductionmentioning

confidence: 99%

PPARβ/δ Agonism Upregulates Forkhead Box A2 to Reduce Inflammation in C2C12 Myoblasts and in Skeletal Muscle

Phua

Tan

Yip

et al. 2020

IJMS

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Daily activities expose muscles to innumerable impacts, causing accumulated tissue damage and inflammation that impairs muscle recovery and function, yet the mechanism modulating the inflammatory response in muscles remains unclear. Our study suggests that Forkhead box A2 (FoxA2), a pioneer transcription factor, has a predominant role in the inflammatory response during skeletal muscle injury. FoxA2 expression in skeletal muscle is upregulated by fatty acids and peroxisome proliferator-activated receptors (PPARs) but is refractory to insulin and glucocorticoids. Using PPARβ/δ agonist GW501516 upregulates FoxA2, which in turn, attenuates the production of proinflammatory cytokines and reduces the infiltration of CD45+ immune cells in two mouse models of muscle inflammation, systemic LPS and intramuscular injection of carrageenan, which mimic localized exercise-induced inflammation. This reduced local inflammatory response limits tissue damage and restores muscle tetanic contraction. In line with these results, a deficiency in either PPARβ/δ or FoxA2 diminishes the action of the PPARβ/δ agonist GW501516 to suppress an aggravated inflammatory response. Our study suggests that FoxA2 in skeletal muscle helps maintain homeostasis, acting as a gatekeeper to maintain key inflammation parameters at the desired level upon injury. Therefore, it is conceivable that certain myositis disorders or other forms of painful musculoskeletal diseases may benefit from approaches that increase FoxA2 activity in skeletal muscle.

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An aPPARent Functional Consequence in Skeletal Muscle Physiology via Peroxisome Proliferator-Activated Receptors

Cited by 59 publications

References 221 publications

From Pre-Diabetes to Diabetes: Diagnosis, Treatments and Translational Research

From Pre-Diabetes to Diabetes: Diagnosis, Treatments and Translational Research

Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments

PPARβ/δ Agonism Upregulates Forkhead Box A2 to Reduce Inflammation in C2C12 Myoblasts and in Skeletal Muscle

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